Introduction
Methods
Medical Research Council Cognitive Function and Ageing Study
Postmortem procedure and anatomical sampling
Immunocytochemistry for alpha-synuclein, quantification
Neuropathology group
|
Criteria
|
Number
| |
---|---|---|---|
No pathology | No AS; Braak stages I-III NFT | 49 | |
NFT only | No AS; Braak stages IV-VI NFT | 43 | |
AS | At least 1 LB or LN in any region | 84 | |
AS | + high NFT | AS + Braak stages IV-VI NFT | 32 |
AS | + low NFT | AS + Braak stages I-III NFT | 52 |
AS DLB | + high NFT | AS pattern consistent with DLB Consensus; Braak stages IV-VI NFT | 13 |
AS DLB | + low NFT | AS pattern consistent with DLB Consensus; Braak stages I-III NFT | 20 |
AS Amygdala-predominant | + high NFT | amygdala-predominant AS pattern: Braak stages IV-VI NFT | 9 |
AS Amygdala-predominant | + low NFT | amygdala-predominant AS pattern: Braak stages I-III NFT | 9 |
AS Other pattern | + high NFT | AS pattern not consistent with DLB consensus or amygdala-predominant AS; Braak stages IV-VI NFT | 10 |
AS Other pattern | + low NFT | AS pattern not consistent with DLB consensus or amygdala-predominant AS: Braak stages I-III NFT | 23 |
Dementia and other outcomes
Specific neuropsychological measures
Statistical analysis
Results
Demographics and AS staging patterns of the study cohort
Demographic characteristic
|
All MRC CFAS (Number = 451)
|
Cambridgeshire and Nottingham cohorts (Number = 208)
|
NFT only (Number = 43)
|
AS + NFT (Number = 32)
|
AS only (Number= 52)
| |||||
---|---|---|---|---|---|---|---|---|---|---|
Sex | ||||||||||
Men | 188 | (41) | 123 | (59) | 10 | (23) | 16 | (50) | 21 | (40) |
Women | 268 | (59) | 85 | (41) | 33 | (74) | 16 | (50) | 31 | (60) |
Age at death | ||||||||||
70 to 79 | 89 | (19) | 40 | (19) | 5 | (12) | 4 | (12) | 15 | (29) |
80 to 89 | 204 | (49) | 102 | (49) | 19 | (44) | 16 | (50) | 28 | (54) |
90 to 105 | 163 | (32) | 66 | (32) | 19 | (44) | 12 | (48) | 9 | (17) |
Education | ||||||||||
<10 years | 318 | (69) | 159 | (76) | 33 | (77) | 26 | (81) | 35 | (67) |
10+ years | 138 | (31) | 49 | (24) | 10 | (23) | 6 | (19) | 17 | (33) |
Social class | ||||||||||
Non manual | 165 | (36) | 79 | (38) | 17 | (39) | 12 | (37) | 17 | (33) |
Manual | 234 | (51) | 110 | (33) | 21 | (49) | 16 | (50) | 30 | (58) |
Unclassified/Army | 57 | (13) | 19 | (9) | 5 | (12) | 4 | (13) | 5 | (9) |
Dementia statusa
| ||||||||||
Dementia | 242 | (53) | 105 | (50) | 30 | (70) | 24 | (75) | 18 | (34) |
No dementia | 184 | (40) | 83 | (40) | 12 | (28) | 6 | (19) | 27 | (53) |
Unknownb
| 30 | (7) | 20 | (10) | 1 | (2) | 2 | (6) | 7 | (13) |
AS and dementia or features of DLB
Brain area
|
% (brains showing AS)
| |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
No PD (n = 201)
|
PD (n = 7)
|
OR (95% CI)
|
P
|
No VH (n = 196)
|
VH (n = 12)
|
OR (95% CI)
|
P
|
No AH (n = 194)
|
AH (n = 14)
|
OR (95% CI)
|
P
| |
Substantia nigra | 11 | 50 | 7.8 (1.0 to 60.6) | <0.01 | 12 | 30 | 3.2 (0.5 to 15.5) | 0.09 | 11 | 31 | 3.5 (0.7 to 13.9) | 0.04 |
Vagus nucleus | 21 | 43 | 2.9 (0.4 to 17.8) | >0.2 | 21 | 25 | 1.2 (0.2 to 5.3) | >0.2 | 22 | 36 | 2.2 (0.5 to 7.8) | >0.2 |
Amygdala | 22 | 57 | 4.7 (0.7 to 33.4) | 0.03 | 22 | 45 | 3.0 (0.7 to 12.3) | 0.07 | 22 | 36 | 1.9 (0.5 to 6.9) | >0.2 |
Frontal cortex | 2 | 0 | 2 | 0 | 2 | 0 | ||||||
Temporal cortex | 2 | 0 | 2 | 8 | 4.0 (0.1 to 44.2) | >0.2 | 2 | 0 | ||||
Parietal cortex | 3 | 29 | 11.1 (0.9 to 82.3) | <0.01 | 4 | 8 | 2.1 (0.04 to 18.5) | >0.2 | 4 | 7 | 1.8 (0.04 to 15.2) | >0.2 |
Hippocampus | 2 | 0 | 2 | 0 | 2 | 0 | ||||||
Entorhinal cortex | 6 | 0 | 2.1 (0.04 to 18.2) | >0.2 | 7 | 0 | 6 | 7 | 1.2 (0.02 to 9.1) | >0.2 | ||
Cingulate cortex | 3 | 14 | 5.4 (0.1 to 57.2) | >0.2 | 3 | 8 | 2.9 (0.05 to 27.1) | >0.2 | 3 | 7 | 2.4 (0.05 to 22.2) | >0.2 |
Association between AS staging pattern and neuropsychological symptoms
Neuropsychological measure
|
High NFT only
|
AS + high NFT
|
AS + low NFT
| ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
n
|
N
|
OR 95% CI
|
P
|
n
|
N
|
OR 95% CI
|
P
|
n
|
N
|
OR 95% CI
| |
MMSE score <21 | 32 | 43 | 3.53 (1.30 - 10.01) | <0.01 | 23 | 32 | 2.21 (0.81 - 6.27) | >0.2 | 25 | 52 | 0.96 (0.41 - 2.26) |
Dementia | 30 | 43 | 3.68 (1.37 - 10.08) | <0.01 | 24 | 32 | 4.63 (1.52 - 15.07) | <0.01 | 17 | 52 | 0.88 (0.35 - 2.22) |
Low CAMCOG Attention | 25 | 43 | 1.29 (0.41 - 4.27) | >0.2 | 15 | 32 | 0.69 (0.21 - 2.32) | >0.2 | 23 | 52 | 0.56 (0.20 - 1.54) |
Low CAMCOG Languagea
| 27 | 43 | 2.05 (0.56 - 8.46) | >0.2 | 21 | 32 | 1.99 (0.49 - 9.68) | >0.2 | 26 | 52 | 0.7 (0.24 - 2.02) |
Low CAMCOG Abstract thinking | 18 | 43 | 1.93 (0.68 - 5.51) | >0.2 | 13 | 32 | 1.62 (0.53 - 5.02) | >0.2 | 20 | 52 | 1.5 (0.57 - 4.00) |
Low CAMCOG Perception | 27 | 43 | 2.33 (0.70 - 8.47) | >0.2 | 16 | 32 | 0.83 (0.27 - 2.63) | >0.2 | 31 | 52 | 2.01 (0.66 - 6.39) |
Low CAMCOG Totalb
| 29 | 43 | 3.67 (0.83 - 22.20) | >0.2 | 19 | 32 | 1.44 (0.38 - 6.13) | >0.2 | 26 | 52 | 0.82 (0.28 - 2.43) |
DLB Consensus + high NFT
|
Amygdala-predominant + high NFT
|
other AS pattern + high NFT
| |||||||||
MMSE score <21 | 10 | 13 | 3.21 (0.70 - 19.89) | >0.2 | 7 | 9 | 2.24 (0.44 - 14.76) | >0.2 | 6 | 10 | 1.44 (0.30 - 7.77) |
Dementia | 10 | 13 | 4.5 (0.96 - 28.04) | 0.06 | 7 | 9 | 4.72 (0.77 - 49.99) | 0.07 | 7 | 10 | 4.72 (0.77 - 49.99) |
Low CAMCOG Attention | 7 | 13 | 1.45 (0.23 - 16.15) | >0.2 | 4 | 9 | 0.41 (0.07 - 2.66) | >0.2 | 4 | 10 | 0.55 (0.08 - 4.40) |
Low CAMCOG Languagea
| 9 | 13 | 3.41 (0.38 -163.00) | >0.2 | 7 | 9 | 2.66 (0.28-130.36) | >0.2 | 5 | 10 | 0.95 (0.13 - 11.36) |
Low CAMCOG Abstract thinking | 4 | 13 | 1.2 (0.20 - 6.54) | >0.2 | 5 | 9 | 1.88 (0.34 - 10.87) | >0.2 | 4 | 10 | 2 (0.29 - 15.30) |
Low CAMCOG Perception | 8 | 13 | 2.07 (0.34 - 22.35) | >0.2 | 5 | 9 | 0.65 (0.12 - 3.85) | >0.2 | 3 | 10 | 0.39 (0.05 - 2.71) |
Low CAMCOG Totalb
| 8 | 13 | 3.03 (0.33 -146.68) | >0.2 | 5 | 9 | 0.63 (0.10 - 4.81) | >0.2 | 6 | 10 | 2.28 (0.23-114.05) |
DLB Consensus + low NFT
|
Amygdala-predominant + low NFT
|
other AS pattern + low NFT
| |||||||||
MMSE score <21 | 13 | 20 | 1.39 (0.45 - 4.38) | >0.2 | 1 | 9 | 0.12 (0.00 - 1.04 ) | >0.2 | 11 | 23 | 1.32 (0.40 - 4.46) |
Dementia | 12 | 20 | 3.24 (0.87 - 13.47) | 0.09 | 0 | 9 | 0 (0.00 - 0.62) | >0.2 | 5 | 23 | 0.56 (0.13 - 2.09) |
Low CAMCOG Attention | 10 | 20 | 0.83 (0.20 - 3.78) | >0.2 | 1 | 9 | 0.07 (0.00 - 0.70) | >0.2 | 12 | 23 | 0.83 (0.22 - 3.35) |
Low CAMCOG Languagea
| 9 | 20 | 0.57 (0.14 - 2.45) | >0.2 | 5 | 9 | 0.95 (0.13 - 11.36) | >0.2 | 12 | 23 | 0.76 (0.20 - 3.11) |
Low CAMCOG Abstract thinking | 6 | 20 | 1 (0.24 - 3.91) | >0.2 | 2 | 9 | 0.6 (0.05 - 4.29) | >0.2 | 12 | 23 | 3 (0.82 -11.68) |
Low CAMCOG Perception | 9 | 20 | 0.93 (0.23 - 4.26) | >0.2 | 6 | 9 | 3.11 (0.32-153.14) | >0.2 | 16 | 23 | 4.15 (0.77 - 41.44) |
Low CAMCOG Totalb
| 7 | 20 | 0.44 (0.10 - 2.01) | >0.2 | 6 | 9 | 2.28 (0.23-114.05) | >0.2 | 13 | 23 | 0.99 (0.25 - 4.38) |